Multi-layer coaxial vaso-occlusive device

ABSTRACT

A vaso-occlusive device includes inner, intermediate, and outer elements arranged coaxially. The inner element is a filamentous element, preferably a microcoil. The intermediate element is made of a non-metallic material, preferably an expansile polymer. The outer element is substantially non-expansile and defines at least one gap or opening through which the intermediate element is exposed. In a preferred embodiment, when the intermediate element is expanded, it protrudes through the at least one gap or opening in the outer element and assumes a configuration with an undulating, convexly-curved outer surface defining a chain of arcuate segments, each having a diameter significantly greater than the diameter of the outer element. The expanded configuration of the intermediate element minimizes friction when the device is deployed through a microcatheter, thereby reducing the likelihood of buckling while maintaining excellent flexibility. The result is a device with enhanced pushability and trackability when deployed through a microcatheter.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in-Part of co-pending applicationSer. No. 10/631,981; filed Jul. 31, 2003, which prior application claimsthe benefit, under 35 U.S.C. Section 119(e), of provisional applicationNo. 60/400,103, filed Jul. 31, 2002, the disclosure of which isincorporated herein by reference.

FEDERALLY-SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

BACKGROUND

This invention relates to vaso-occlusive devices, such as vaso-occlusivecoils and the like, for the embolization of vascular aneurysms andsimilar vascular abnormalities. Specifically, the invention is animprovement over existing two layer or two element coaxialvaso-occlusive devices, particularly those having a polymer coating orcovering. In particular, the present invention is a three layer or threeelement coaxial vaso-occlusive device that provides improved durability,pushability, and trackability inside a microcatheter. The characteristictermed “trackability” relates to the ease of advancing oneinterventional device within or over another, and it is related tofriction and flexibility.

Vaso-occlusive devices are typically used within the vasculature of thehuman body to block the flow of blood through a vessel through theformation of an embolus. Vaso-occlusive devices are also used to form anembolus within an aneurysm stemming from the vessel. Vaso-occlusivedevices can be formed of one or more elements, generally delivered intothe vasculature via a catheter or similar mechanism.

The embolization of blood vessels is desired in a number of clinicalsituations. For example, vascular embolization has been used to controlvascular bleeding, to occlude the blood supply to tumors, and to occludevascular aneurysms, particularly intracranial aneurysms. In recentyears, vascular embolization for the treatment of aneurysms has receivedmuch attention. Several different treatment modalities have beenemployed in the prior art. One approach that has shown promise is theuse of thrombogenic microcoils. These microcoils may be made of abiocompatible metal alloy (typically platinum and tungsten) or asuitable polymer. If made of metal, the coil may be provided with Dacronfibers to increase thrombogenicity. The coil is deployed through amicrocatheter to the vascular site. Examples of microcoils are disclosedin the following U.S. Pat. No. 4,994,069—Ritchart et al.; U.S. Pat. No.5,133,731—Butler et al.; U.S. Pat. No. 5,226,911—Chee et al.; U.S. Pat.No. 5,312,415—Palermo; U.S. Pat. No. 5,382,259—Phelps et al.; U.S. Pat.No. 5,382,260—Dormandy, Jr. et al.; U.S. Pat. No. 5,476,472—Dormandy,Jr. et al.; U.S. Pat. No. 5,578,074—Mirigian; U.S. Pat. No.5,582,619—Ken; U.S. Pat. No. 5,624,461—Mariant; U.S. Pat. No.5,645,558—Horton; U.S. Pat. No. 5,658,308—Snyder; and U.S. Pat. No.5,718,711—Berenstein et al.

A specific type of microcoil that has achieved a measure of success isthe Guglielmi Detachable Coil (“GDC”), described in U.S. Pat. No.5,122,136—Guglielmi et al. The GDC employs a platinum wire coil fixed toa stainless steel delivery wire by a solder connection. After the coilis placed inside an aneurysm, an electrical current is applied to thedelivery wire, which electrolytically disintegrates the solder junction,thereby detaching the coil from the delivery wire. The application ofthe current also creates a positive electrical charge on the coil, whichattracts negatively-charged blood cells, platelets, and fibrinogen,thereby increasing the thrombogenicity of the coil. Several coils ofdifferent diameters and lengths can be packed into an aneurysm until theaneurysm is completely filled. The coils thus create and hold a thrombuswithin the aneurysm, inhibiting its displacement and its fragmentation.

The advantages of the GDC procedure are the ability to withdraw andrelocate the coil if it migrates from its desired location, and theenhanced ability to promote the formation of a stable thrombus withinthe aneurysm.

A more recent development in the field of microcoil vaso-occlusivedevices is exemplified in U.S. Pat. No. 6,299,619—Greene, Jr. et al. andU.S. Pat. No. 6,602,261—Greene, Jr. et al., both assigned to theassignee of the subject invention. These patents disclose vaso-occlusivedevices comprising a microcoil with one or more expansile elementsdisposed on the outer surface of the coil. The expansile elements may beformed of any of a number of expansile polymeric hydrogels, oralternatively, environmentally-sensitive polymers that expand inresponse to a change in an environmental parameter (e.g., temperature orpH) when exposed to a physiological environment, such as the bloodstream.

While the microcoils with expansile elements have exhibit great promisein, for example, embolizing aneurysms of a wide variety of sizes andconfigurations, the expansile elements increase the frictional forcesbetween the vaso-occlusive device and a microcatheter through which thedevice is deployed. Furthermore, depending on the configuration andmaterial of the expansile elements, the flexibility of the device may bereduced. These factors may result in a device that has less than optimalpushability (resistance to buckling) and reduced trackability (asdefined above).

There has thus been a long-felt, but as yet unsatisfied need for amicrocoil vaso-occlusive device that has all the advantages of theexpansile element type of device, and that also exhibits enhancedpushability and trackability, with good durability characteristics.

SUMMARY OF THE INVENTION

Broadly, the present invention is a vaso-occlusive device, comprisingthree coaxial elements: an elongate, flexible, filamentous innerelement; a non-metallic intermediate element coaxially surrounding theinner element and in intimate contact therewith; and an outer elementcoaxially surrounding the intermediate element and in intimate contacttherewith, the outer element including one or more openings or gapsthrough which the intermediate element is exposed.

In one preferred embodiment of the invention, the inner element is inthe form of a helical coil made of a biocompatible, radiopaque metal,and the intermediate element is a conformal coating or layer on theinner element, the conformal coating or layer being made of a softpolymeric material that is preferably an expansile polymer.Advantageously, the polymeric hydrogel is an environmentally-responsivehydrogel that expands upon exposure to the physiological environment,for example, of the blood stream. The polymer may advantageously bebio-absorbable or biodegradable.

The outer element is advantageously a helical “over-coil” that isloosely wound (“open-wound”) over the intermediate element, except atproximal and distal end sections, where it is tightly wound(“close-wound”). The close-wound proximal and distal end sectionssupport the inner element, protecting it from damage during deploymentand any necessary repositioning, while also securely binding theintermediate element to the inner element at the proximal and distalends of the device and restraining the hydrogel of the intermediateelement from expanding at the respective ends of the device. Theopen-wound section between the proximal and distal end sections createsa single, continuous helical opening through which the intermediateelement expands. The helical configuration of the opening forces theexpanded polymeric intermediate element to assume the configuration of achain of arcuate segments protruding radially outwardly between thecoils of the over-coil, rather than that of a continuous polymeric layerhaving a continuous, uninterrupted exterior surface. Because each of thearcuate segments contacts the interior surface of a microcatheter (e.g.,during deployment) primarily at or near a tangential contact point, thetotal contact area of the intermediate element is reduced as compared toa continuous axial polymeric element. This reduced contact areacorrespondingly reduces the aggregate friction between the polymericlayer and the microcatheter, thereby decreasing the resistance tomanipulation of the device. The open-wound section also creates hingepoints between the arcuate segments of the polymeric intermediateelement, thereby increasing the overall flexibility of the device.

It has been confirmed experimentally that the reduced friction andincreased flexibility afforded by the outer element, and by theinteraction between the outer and intermediate elements, enhances theboth the pushability and trackability of a device made in accordancewith the present invention, as compared, for example, with prior artmicrocoil devices having expansile polymeric coatings or elements on oralong their exterior surfaces.

The invention thus provides a microcoil vaso-occlusive device with anexpansile element that allows the device to embolize very efficiently awide variety of vascular abnormalities, e.g., aneurysms of a widevariety of shapes, sizes, and locations, and yet that exhibits enhancedpushability and trackability as compared to the prior art.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a vaso-occlusive device in accordancewith a preferred embodiment of the present invention;

FIG. 2 is an axial cross-sectional view of the device of FIG. 1;

FIG. 3 is a perspective view, similar to that of FIG. 1, showing theexpansile polymeric intermediate element in its expanded state;

FIG. 4 is an axial cross-sectional view of FIG. 3;

FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 2, butshowing a first variant form of the invention, in which the innerelement comprises two coaxial helical microcoils;

FIG. 6 is a cross-sectional view similar to that of FIG. 5, but showinga second variant form of the invention, in which the inner elementcomprises three coaxial helical microcoils;

FIG. 7 is a cross-sectional view similar to that of FIG. 5, but showinga third variant form of the invention, in which the inner elementcomprises a helical microcoil defining a lumen containing a solidcoaxial core;

FIG. 8 is a cross-sectional view similar to that of FIG. 5, but showinga fourth variant form of the invention, in which the inner elementcomprises a helical microcoil defining a lumen containing a hollow,tubular coaxial core; and

FIG. 9 is a perspective view of an alternative embodiment of theinvention.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIGS. 1-4, a vaso-occlusive device 10, in accordance with apreferred embodiment of the invention, comprises three elongate, coaxialelements: an inner element 11, a non-metallic intermediate element 12,and a non-expansile outer element 13 that covers at least a portion ofthe intermediate element. The intermediate element 12 is in intimatecontact with both the inner element 11 and the outer element 13.

The inner element 11 is formed of a flexible, elongate filament or wirethat is preferably made of a material that allows visualization undervarious medical imaging means, such as X-ray, MRI, or ultrasound.Preferably, the inner element 11 is formed from a length of wire made ofany of various biocompatible, radiopaque metals, such as platinum,tantalum, tungsten, gold, titanium, nitinol, stainless steel, Elgiloy(cobalt-chromium-nickel), or other suitable alloys known in the art.Alternatively, it can be made from or include non-metallic materials,such as polymers, collagen, proteins, drugs, biologic materials (e.g.,cellular material and genes), bioactive agents, therapeutic compounds,or combinations of these materials. If made of a non-radiopaquematerial, it should advantageously be doped or impregnated or chemicallymodified to be visible with one or more imaging techniques.Alternatively, it can be made of a material that is highly visible bymeans of MRI or ultrasound. The inner element 11 can be formed invarious configurations, including, but not limited to, coils, rods,tubes, cables, braids, cut tubes, or other elongate, flexible forms. Asshown, it is in the form of a helical coil, which may be preferred. Inone specific embodiment, it is formed at least in part of a multi-filarcoil configuration, as described in the co-owned U.S. Patent ApplicationPublication No. 2004/0006362, the disclosure of which is incorporatedherein by reference.

The intermediate element 12 may be formed as a coating, wrapping,tubular sleeve, or other construction to create a substantiallycontinuous surface coaxially around the inner element 11. Alternatively,it can be formed into a cylinder and then skewered onto the inner coreelement 11, as described in the co-owned and co-pending U.S. PatentApplication Publication No. 2002/0177855, the disclosure of which isincorporated herein by reference. The intermediate element 12 preferablycovers all of the length of the inner element 11, except for shortproximal and distal sections.

The intermediate element 12 may be made of any of various suitable,substantially non-metallic, biocompatible materials, including polymers,biopolymers, biologic materials, and combinations of these materials.Suitable polymers include cellulose, polypropylene,polyvinylpyrrolidone, polyacrylics, polylactides, polyamides, polyvinylalcohol (PVA), polyester, polyurethane, polyglycolic acid,polyfluorocarbons (e.g., PTFE), nylon, polymethylmethacrylate (PMMA),hydrogels, and silicones. Exemplary biologic materials includealginates, hyaluronic acid, fibrin, collagen and silk. Optionally, theintermediate element 12 can be impregnated, grafted, bound, or modifiedto deliver therapeutic compounds, drugs, collagen, proteins, genes,bioactive agents, or cellular material. See, e.g., U.S. Pat. No.5,658,308 and International Publications Nos. WO 99/65401 and WO00/27445, the disclosures of which are incorporated herein by reference.In one preferred embodiment, the intermediate element 12 is made of astate-of-the-art bioabsorbable or biodegradable polymer, such as, forexample, those described in U.S. Patent Application Publications Nos.2002/0040239 and 2002/0020417, the disclosures of which are incorporatedherein by reference. In another preferred embodiment, the intermediateelement 12 is made of a soft conformal material, and more preferably ofan expansile material such as a hydrogel.

The most preferred material is an environmentally responsive hydrogel,such as that described in U.S. Patent Application Publication No.2002/0176880, the disclosure of which is incorporated herein byreference. Specifically, the hydrogels described in U.S. PatentApplication Publication No. 2002/0176880 are of a type that undergoescontrolled volumetric expansion in response to changes in suchenvironmental parameters as pH or temperature. These hydrogels areprepared by forming a liquid mixture that contains (a) at least onemonomer and/or polymer, at least a portion of which is sensitive tochanges in an environmental parameter; (b) a cross-linking agent; and(c) a polymerization initiator. If desired, a porosigen (e.g., NaCl, icecrystals, or sucrose) may be added to the mixture, and then removed fromthe resultant solid hydrogel to provide a hydrogel with sufficientporosity to permit cellular ingrowth. The controlled rate of expansionis provided through the incorporation of ethylenically unsaturatedmonomers with ionizable functional groups (e.g., amines, carboxylicacids). For example, if acrylic acid is incorporated into thecrosslinked network, the hydrogel is incubated in a low pH solution toprotonate the carboxylic acids. After the excess low pH solution isrinsed away and the hydrogel dried, the hydrogel can be introducedthrough a microcatheter filled with saline at physiological pH or withblood. The hydrogel cannot expand until the carboxylic acid groupsdeprotonate. Conversely, if an amine-containing monomer is incorporatedinto the crosslinked network, the hydrogel is incubated in a high pHsolution to deprotonate amines. After the excess high pH solution isrinsed away and the hydrogel dried, the hydrogel can be introducedthrough a microcatheter filled with saline at physiological pH or withblood. The hydrogel cannot expand until the amine groups protonate.

More specifically, in a preferred formulation of the hydrogel, themonomer solution is comprised of ethylenically unsaturated monomers, anethylenically unsaturated crosslinking agent, a porosigen, and asolvent. At least a portion, preferably 10%-50%, and more preferably10%-30%, of the monomers selected must be pH sensitive. The preferred pHsensitive monomer is acrylic acid. Methacrylic acid and derivatives ofboth acids will also impart pH sensitivity. Since the mechanicalproperties of hydrogels prepared exclusively with these acids are poor,a monomer to provide additional mechanical properties should beselected. A preferred monomer for providing mechanical properties isacrylamide, which may be used in combination with one or more of theabove-mentioned pH sensitive monomers to impart additional compressivestrength or other mechanical properties. Preferred concentrations of themonomers in the solvent range from 20% w/w to 30% w/w.

The crosslinking agent can be any multifunctional ethylenicallyunsaturated compound, preferably N,N′-methylenebisacrylamide. Ifbiodegradation of the hydrogel material is desired, a biodegradablecrosslinking agent should be selected. The concentrations of thecrosslinking agent in the solvent should be less than about 1% w/w, andpreferably less than about 0.1% w/w.

The porosity of the hydrogel material is provided by a supersaturatedsuspension of a porosigen in the monomer solution. A porosigen that isnot soluble in the monomer solution, but is soluble in the washingsolution can also be used. Sodium chloride is the preferred porosigen,but potassium chloride, ice, sucrose, and sodium bicarbonate can also beused. It is preferred to control the particle size of the porosigen toless than about 25 microns, more preferably less than about 10 microns.The small particle size aids in the suspension of the porosigen in thesolvent. Preferred concentrations of the porosigen range from about 5%w/w to about 50% w/w, more preferably about 10% w/w to about 20% w/w, inthe monomer solution. Alternatively, the porosigen can be omitted and anon-porous hydrogel can be fabricated.

The solvent, if necessary, is selected based on the solubilities of themonomers, crosslinking agent, and porosigen. If a liquid monomer (e.g.2-hydroxyethyl methacrylate) is used, a solvent is not necessary. Apreferred solvent is water, but ethyl alcohol can also be used.Preferred concentrations of the solvent range from about 20% w/w toabout 80% w/w, more preferably about 50% w/w to about 80% w/w.

The crosslink density substantially affects the mechanical properties ofthese hydrogel materials. The crosslink density (and hence themechanical properties) can best be manipulated through changes in themonomer concentration, crosslinking agent concentration, and solventconcentration. The crosslinking of the monomer can be achieved throughreduction-oxidation, radiation, and heat. Radiation crosslinking of themonomer solution can be achieved with ultraviolet light and visiblelight with suitable initiators or ionizing radiation (e.g. electron beamor gamma ray) without initiators. A preferred type of crosslinkinginitiator is one that acts via reduction-oxidation. Specific examples ofsuch red/ox initiators that may be used in this embodiment of theinvention are ammonium persulfate andN,N,N′,N′-tetramethylethylenediamine.

After the polymerization is complete, the hydrogen is washed with water,alcohol or other suitable washing solution(s) to remove theporosigen(s), any unreacted, residual monomer(s) and any unincorporatedoligomers. Preferably this is accomplished by initially washing thehydrogel in distilled water.

As discussed above, the control of the expansion rate of the hydrogel isachieved through the protonation/deprotonation of ionizable functionalgroups present on the hydrogel network. Once the hydrogel has beenprepared and the excess monomer and porosigen have been washed away, thesteps to control the rate of expansion can be performed.

In embodiments where pH sensitive monomers with carboxylic acid groupshave been incorporated into the hydrogel network, the hydrogel isincubated in a low pH solution. The free protons in the solutionprotonate the carboxylic acid groups on the hydrogel network. Theduration and temperature of the incubation and the pH of the solutioninfluence the amount of control on the expansion rate. Generally, theduration and temperature of the incubation are directly proportional tothe amount of expansion control, while the solution pH is inverselyproportional. It has been determined that the water content of thetreating solution also affects the expansion control. In this regard,the hydrogel is able to expand more in the treating solution and it ispresumed that an increased number of carboxylic acid groups areavailable for protonation. An optimization of water content and pH isrequired for maximum control on the expansion rate. After the incubationis concluded, the excess treating solution is washed away and thehydrogel material is dried. The hydrogel treated with the low pHsolution has been observed to dry down to a smaller dimension than theuntreated hydrogel. This is a desired effect since delivery of thesehydrogel materials through a microcatheter is desired.

If pH sensitive monomers with amine groups were incorporated into thehydrogel network, the hydrogel is incubated in high pH solution.Deprotonation occurs on the amine groups of the hydrogel network at highpH. The duration and temperature of the incubation, and the pH of thesolution, influence the amount of control on the expansion rate.Generally, the duration, temperature, and solution pH of the incubationare directly proportional to the amount of expansion control. After theincubation is concluded, the excess treating solution is washed away andthe hydrogel material is dried.

For the embodiment of the vaso-occlusive device having an intermediateelement formed of an expansile polymeric hydrogel, when the intermediateelement 12 expands, the areas of the soft, conformal intermediateelement 12 that are not covered or constrained by the outer element 13extend radially outward through the openings or gaps, or between thecoils of the outer element 13 (as described below) to form an undulatingouter surface comprising a chain of arcuate segments, as a result of theconstraint imposed by the outer element 13. Because the arcuate segmentsof the undulating outer surface contact the interior wall surface of amicrocatheter through which the device is deployed only at or neartangential contact points proximate the apex of each segment, thisundulating or arcuate configuration provides reduced friction ascompared to a continuous or smooth surface of the same material.

The outer element 13 is a flexible, elongate, substantially tubularmember, at least a substantial portion of the length of which, andpreferably most of the length of which, includes or defines at least oneopening or gap to allow the exposure and/or protrusion of theintermediate element 12. Suitable configurations for the outer element13 include helical coils, braids, and slotted or spiral-cut tubes. Theouter element 13 may be made of any suitable biocompatible metal orpolymer, including those listed above for the inner element 11. Forthose embodiments using a soft, conformal intermediate element 12, theouter element 13 should have sufficient radial strength to compress orrestrain the intermediate element 12.

Preferably, the openings in the outer element 13 are such that, along asubstantial portion of the length of the device, the open area of theouter element 13 is at least about 20%, and more preferably, more thanabout 40%, of the total external surface area of the device between theproximal and distal limits of that portion of the device length. Forexample, near the ends of the device, the outer element 13 may have arelatively low percentage of open area (i.e., less than about 20%),while for the greater part of the length of the device between the endportions thereof, a greater percentage (i.e., at least about 20%, andpreferably more than about 40%) of the outer element 13 may be open,allowing a greater exposure of the intermediate element 12 through theouter element 13. Preferably, the portion of the outer element 13covering at least about 75% of the overall length of the device willhave the greater percentage of open area.

In the most preferred embodiment, the device comprises an inner element11 formed of a tightly-wound (“close-wound”) helical coil of abiocompatible metal wire (e.g., platinum alloy), an intermediate element12 of a hydrophilic expansile polymer (e.g., hydrogel), and an outerelement 13 in the form of a biocompatible metal or polymer helical coilthat is open-wound for most of its length, with a close-wound proximalend section 14 and a close-wound distal end section 15. The open-woundportion of the outer element 13 defines a single, continuous, helicalopening or gap. The coil is preferably made from a wire that has adiameter of no more than about 0.15 mm. The pitch of the coil of whichthe outer element 13 is comprised may be up to ten times the diameter offilament from which the coil is wound, and preferably between about 5percent and about 100 percent greater than the diameter of the filament.

A coupling element 16 is advantageously attached to the proximal end ofthe inner element 11 for detachable attachment to a deployment device(not shown). A rounded obturator tip 17 may be attached to the distalend of the inner element 11.

In the above-described most preferred embodiment, the hydrogel of theintermediate element 12 expands or swells upon exposure to an aqueousenvironment (e.g., blood). Preferably, the hydrogel expands to betweenabout two times and about 20 times its original volume. As shown inFIGS. 3 and 4, the swollen or expanded intermediate element 12 protrudesthrough the helical opening or gap defined between the coils of theopen-wound section of the outer element 13 to form an undulating,convexly-curved surface defining a chain of arcuate or rounded segments,each having a diameter that is substantially greater than the diameterof the outer element 13.

The helical outer element 13 described above may be considered asdefining a single, helical opening or gap, or it may be viewed asdefining a plurality of connected openings or gaps, each defined betweenan adjacent pair of windings of the coil of the outer element 13.Alternatively, if the outer element 13 is formed as a slotted tube, forexample, the outer element 13 will be seen to define a plurality ofdiscrete openings or gaps in its axial middle section that arefunctionally equivalent to the helical opening(s) defined in theillustrated embodiment.

The device 10 can be constructed with various radial thickness of eachcoaxial element to provide different handling characteristics.Preferably, the inner element 11 has a diameter of between about 0.075mm and 0.75 mm; the intermediate element 12 has a thickness of betweenabout 0.025 mm and 1.00 mm; and the outer element 13 has a thickness ofbetween about 0.025 mm and 0.25 mm. For the embodiments that use anexpansile intermediate element 12, these thicknesses are measured in thenon-expanded state. Preferably, the outer diameter of the outer element13 is actually somewhat less than the expanded or swollen diameter ofthe intermediate element 12, so that the latter will readily expandthrough the openings or gaps in the outer element 13.

FIGS. 5 and 6 illustrate variants of the preferred embodiment of theinvention, with multilayer structures for the inner element.Specifically, FIG. 5 shows a first variant having an inner elementcomprising first and second coaxial coils 110 a, 110 b, respectively.FIG. 6 shows a second variant having an inner element comprising first,second, and third coaxial coils 210 a, 210 b, and 210 c, respectively.Suitable coaxial coil structures and their methods of manufacture aredisclosed in commonly owned and co-pending U.S. Patent ApplicationPublication No. 2004/0006363, the disclosure of which is incorporatedherein by reference. The inner element may, in fact, comprise four ormore coaxial layers. Similarly, the outer element 13 may comprisemultiple coaxial helical coil layers, provided that a suitablepercentage of the surface area of the outer element remains open for theexposure of the intermediate element, as explained above.

FIG. 7 illustrates a third variant of the present invention, in whichthe inner element comprises a helical coil 310 defining an axial lumen,at least a substantial portion of the length of which is filled with asolid core member 320. The solid core member 320 may be impregnated witha therapeutic agent that can be absorbed into the bloodstream.

FIG. 8 illustrates a fourth variant of the invention, in which the innerelement comprises a helical coil 410 defining an axial lumen, at least asubstantial portion of which contains a hollow, tubular core member 420.The tubular core member 340 provides additional strength, and it may befilled with a liquid therapeutic agent (not shown).

FIG. 9 shows a vaso-occlusive device 10′ in accordance with analternative embodiment of the invention. This embodiment includes anouter element 13′ with a distal section 15′ that is not close wound, butis, instead, made with small gaps of approximately 5% to 100% of thediameter of the wire or filament of which the outer element 13′ is made.These gaps make the distal section 15′ of the device 10′ more flexiblein the area where the outer element 13′ overlaps the inner element 11′.

In the embodiment shown in FIG. 9, the proximal ends of both the innerelement 11′ and the outer element 13′ are both advantageously attachedto a coupling element 16′ by soldering or welding. The attachment ofboth the inner element 11′ and the outer element 13′ to the couplingelement 16′ makes the proximal end of the device 10′ more resistant todeformation during deployment and implantation.

In any of the embodiments described above, a portion of the outerelement and/or a portion of the intermediate element may be modified (asby coating, for example) to include structure that promotes the adhesionof beneficial cells or growth factors. An exemplary coating that be usedfor this purpose is disclosed in U.S. Patent Application Publication No.2002/0049495, the disclosure of which is incorporated herein byreference.

As indicated above, the present invention provides good trackability ina microcatheter. In other words, it is easily advanced through acatheter without binding against or moving the catheter. This advantageis achieved through reduced friction and reduced buckling at the ends ofthe device. The force required to advance the device through a typicalmicrocatheter would normally be less than about 0.7 lbs.

The device is preferably detachable from a flexible, elongate deliveryapparatus (not shown), such as a wire, a pusher tube, or the like.Exemplary detachment systems known in the art include electrolytic,mechanical, electromechanical, thermal, ultrasonic, and hydraulicdetachment mechanisms. The device may be formed into a secondaryconfiguration, such as a helical coil, a sphere, an ovoid, or any othersuitable two- or three-dimensional shape known in the art ofvaso-occlusive devices. Alternatively, the device can be left in arelatively straight configuration with or without a curvature at the end(such as a “J” configuration).

In any of the above-described embodiments, either the inner element orthe intermediate element, or both, may be formed so as to besubstantially stretch-resistant, so as to limit the stretching of theentire device (including the outer element) if the device needs to bepartially withdrawn for repositioning or the like. It will beappreciated that a number of the materials discussed above will bestretch-resistant to varying degrees.

The device is useful for the occlusion and/or embolization of bloodvessels, other vascular spaces such as aneurysms, and other tubular orsaccular organs or spaces throughout the body. Specific applicationswhere it may be useful include the occlusion of cerebral aneurysms,aortic aneurysms, fistulas, fallopian tubes, cardiac septal defects,patent foramen ovale, and the left atrial appendage of the heart. Forsome of these applications, it may be preferable to use devices withdimensions larger than those specified above.

Although preferred embodiments of the invention have been described inthis specification and the accompanying drawings, it will be appreciatedthat a number of variations and modifications may suggest themselves tothose skilled in the pertinent arts. Thus, the scope of the presentinvention is not limited to the specific embodiments and examplesdescribed herein, but should be deemed to encompass alternativeembodiments and equivalents, as determined by a fair reading of theclaims that follow.

1. A vaso-occlusive device, comprising: an elongate, flexible,filamentous inner element; a non-metallic intermediate element coaxiallysurrounding the inner element and in intimate contact therewith; and anouter element coaxially surrounding the intermediate element, the outerelement defining an open area through which the intermediate element isexposed; wherein along a substantial predetermined portion of the lengthof the device, the open area constitutes at least about 20 percent ofthe surface area of device within the predetermined portion of itslength.
 2. The vaso-occlusive device of claim 1, wherein theintermediate element includes an expansile polymeric material
 3. Thevaso-occlusive device of claim 1, wherein the outer element includes ahelical coil having a pitch that defines the open area through which theintermediate element is exposed.
 4. The vaso-occlusive device of claim3, wherein the coil is formed of a helically-wound filament, and whereinthe pitch of the coil is greater than the diameter of the filament. 5.The vaso-occlusive device of claim 4, wherein the pitch of the coil isbetween about 5 percent and about 100 percent greater than the diameterof the filament.
 6. The vaso-occlusive device of claim 2, wherein theexpansile polymeric material comprises a hydrogel.
 7. The vaso-occlusivedevice of claim 6, wherein the expansile polymeric material consistsessentially of a hydrogel.
 8. The vaso-occlusive device of claim 7,wherein the hydrogel is of a type that expands in response to a changein an environmental parameter.
 9. The vaso-occlusive device of claim 8,wherein the environmental parameter is selected from the groupconsisting of temperature and pH.
 10. The vaso-occlusive device of claim1, wherein the inner element comprises at least two concentricmicrocoils.
 11. The vaso-occlusive device of claim 1, wherein the innerelement defines a lumen containing a hollow, tubular core element. 12.The vaso-occlusive device of claim 1, wherein the inner element definesa lumen containing a substantially solid core element.
 13. Thevaso-occlusive device of claim 1, wherein at least one of the innerelement and the intermediate element includes a material selected fromthe group consisting of at least one of a drug, a bioactive agent, atherapeutic compound, cellular material, genes, collagen, and protein.14. A vaso-occlusive device comprising: a filamentous inner element; anon-metallic intermediate element coaxially surrounding the innerelement and in intimate contact therewith; and an outer elementcoaxially surrounding the intermediate element and having an open areathrough which the intermediate element is exposed, the outer elementcomprising a helically-wound filament defining a helical coil having apitch that is greater than the diameter of the filament.
 15. Thevaso-occlusive device of claim 14, wherein at least one of the inner andintermediate elements is made at least in part of a non-metallicbiocompatible material.
 16. The vaso-occlusive device of claim 15,wherein the pitch of the coil is between about 5 percent and about 100percent greater than the diameter of the filament.
 17. Thevaso-occlusive device of claim 14, wherein the inner element comprises amicrocoil made of a biocompatible material selected from the groupconsisting of metal wire and polymeric filament, and wherein theintermediate element is formed of a biocompatible polymeric material 18.The vaso-occlusive device of claim 14, wherein the intermediate elementincludes an expansile polymeric material
 19. The vaso-occlusive deviceof claim 14, wherein along a substantial predetermined portion of thelength of the device, the open area constitutes at least about 20percent of the surface area of device within the predetermined portionof its length.
 20. The vaso-occlusive device of claim 18, wherein theexpansile polymeric material comprises a hydrogel.
 21. Thevaso-occlusive device of claim 20, wherein the expansile polymericmaterial consists essentially of a hydrogel.
 22. The vaso-occlusivedevice of claim 21, wherein the hydrogel is of a type that expands inresponse to a change in an environmental parameter.
 23. Thevaso-occlusive device of claim 22, wherein the environmental parameteris selected from the group consisting of temperature and pH.
 24. Thevaso-occlusive device of claim 14, wherein the inner element hasproximal and distal ends, and wherein the outer element comprises anopen-wound helical coil portion extending between proximal and distalend sections that are respectively attached to the inner elementadjacent to the proximal and distal ends of the inner element, whereinthe open-wound portion defines the open area.
 25. The vaso-occlusivedevice of claim 14, wherein at least one of the inner element and theintermediate element includes a material selected from the groupconsisting of at least one of a drug, a bioactive agent, a therapeuticcompound, cellular material, genes, collagen, and protein.